Confocal microscopes optically section tissue to produce sectional microscopic images of tissue, referred to herein as confocal images. An example of a confocal microscope is the VivaScope® manufactured by Lucid, Inc. of Rochester, N.Y. Other examples of confocal microscopes are described in U.S. Pat. Nos. 5,788,639, 5,880,880, and 5,995,867, and in articles by Milind Rajadhyaksha et al., “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin provides strong contrast,” The Journal of Investigative Dermatology, Volume 104, No. 6, June 1995, and Milind Rajadhyaksha and James M. Zavislan, “Confocal laser microscope images tissue in vivo,” Laser Focus World, February 1997, pages 119-127. The confocal microscope may image naturally or surgically exposed in-vivo tissue, which is useful to evaluate a lesion in tissue without needing a biopsy and pathological evaluation on slides of histologically prepared, mechanically sectioned, tissue specimens from such biopsy. Also, confocal microscopes are useful for pathological examination of ex-vivo tissue, i.e., tissue removed from a patient, without requiring that such tissue be mechanically sectioned and histologically prepared for viewing on slides with a traditional microscope.
Systems have been developed for obtaining a macroscopic image of tissue for use in locating where sectional microscopic images were imaged in such tissue by a confocal microscope. U.S. Pat. Nos. 6,684,092 and 5,836,877 describe a telepathology system having a camera and confocal imager in a fixed spatial relationship, in which both are presented over the tissue, such that the camera captures a macroscopic image and the confocal imager captures one or more confocal images. Instead of the camera, the confocal imager described in these patents may utilize a different objective lens to obtain the macroscopic image. The locations for imaging by the confocal imager may be selected automatically, or manually by the user using the macroscopic image. The macroscopic image and confocal images taken are then viewable on the display of the computer, in which the location of confocal images may be referenced in the macroscopic image of the tissue.
U.S. Pat. No. 6,411,434 describes a system for imaging ex-vivo tissue in a cassette, where a camera views one side of the tissue to provide a macroscopic image, and on the other side of the tissue is imaged by a confocal microscope. A display can provide an image of both the macroscopic image and confocal images in which the relative location of the microscopic image is indicated by an outlined region in the displayed macroscopic image.
U.S. patent application Ser. No. 10/471,332, filed Feb. 23, 2004, which has priority to International Patent Application No. PCT/US02/07173, published on Sep. 19, 2002 under International Publication No. WO02/073246A2, describes a confocal microscope having a macroscope, and a turret having different objective lens to enable selection of an objective lens for macroscopic imaging or microscopic imaging, in which light from the tissue through the selected objective lens is provided to optics of the macroscope or confocal microscope, respectively. Sites may be marked, such as on a printout, of the macroscopic image, and then using the macroscopic image on a display, the tissue is moved to each site for obtaining sectional microscopic confocal image(s).
Other systems for locating confocal images captured by a confocal microscope have been developed without use of a camera or macroscopic image. For example, U.S. Pat. Nos. 6,424,852 and 6,745,067 each describe a pen or marker mechanically coupled to a translation stage of a confocal microscope to record movements of the stage on a paper pad or recording medium below the pen or marker. U.S. Pat. No. 6,745,067 also describes a system for marking on a physical recording medium located on the tissue, such as a label, after confocal imaging of the tissue is completed, in which the marks placed are in accordance with one or locations of selected confocal images during confocal imaging of the tissue.
Although the above-described systems are useful, it would be desirable if the macroscopic imaging means need not be physically integrated into the confocal microscope, such that the imaging head of the confocal microscope may be made less complex and smaller, and that the spatial relationship between a camera and confocal microscope were mechanically assured by their individual alignment to the same tissue attachment device, so as to facilitate the tracking, targeting, and marking of confocal images in a macroscopic image captured by such camera.
It would further be desirable to provide means for assisting a physician in future examinations of the same tissue to observe possible changes in the condition of the tissue when treatment of the lesion is deferred or is non-invasive.